POS0135 GENETICAL AND PHENOTYPICAL FINDINGS OF CHILDHOOD-ONSET SYSTEMIC LUPUS ERYTHEMATOSUS
Authors: P. Morán Álvarez, C. Passarelli, V. Messia, M. Pardeo, E. Marasco, A. Insalaco, F. De Benedetti, C. Bracaglia
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Systemic lupus erythematosus (SLE) is a systemic autoimmune disease which leads to inflammation and organ damage caused by immune complex deposition. Classically, childhood SLE has been considered as a polygenic autoimmune disease; however, a pediatric monogenic lupus-like phenotype (LL) is emerging due to the recent recognition of several related novel high-penetrance gene variants. This fact associated to the high degree of concordance among monozygotic twins, supports the importance of genetic background in cSLE pathogenesis. <h3>Objectives</h3> To identify the presence of variants in gene related to monogenic lupus and their relationship with clinical manifestations in cSLE or LL. <h3>Methods</h3> A descriptive, observational, cross-sectional study was carried out in children with cSLE or LL. The genetic analysis (Sanger/Clinical Exome Sequencing) was performed from isolated DNA obtained from blood sample. <h3>Results</h3> Forty-five children were included in the study. The genetic analysis detected at least one variant in 14 (31.1%) children, 5 (35.7%) with cSLE and 9 (64.3%) with LL. Of those who carry a genetic variant, the median age at disease onset was 11 years (range: 2-16) and 85.7% were female; most of them Caucasians (85.7%). Seven (50%) and 3 (21.4%) out of 14 patients had a positive family and/or a personal history for autoimmune diseases, respectively. Regarding clinical manifestations at onset, musculoskeletal were the most frequent (10 patients, 71.4%), followed by hematological (9 patients, 64.3%), cutaneous (9 patients, 64.3%), constitutional with fever (8 patients, 57.1%), neurological (7 patients, 50%), renal (5 patients, 35.7%), cardiac (3 patients, 21.4%) and pulmonary (2 patients, 14.3%) manifestations. Related to immunological parameters, 13 (92.8%) were ANA positive, 7 (50%) anti-dsDNA, 4 (28.6%) ENA and 3 (21.4%) aPL positive. Both C3 and C4 were low in 8 (57.1.4%) children and isolated C3 levels were low in 4 (28.6%) patients. Among the variants, we found that only two patients who carry a <i>TREX</i> variant showed normal C3 and C4 levels; one of them presented with lupus pernio as reported in literature. Also, we identified the same <i>RNASEH2B (c.868G&gt;A</i>) variant in two siblings with similar phenotypes and <i>TLR7 (c.1520T&gt;C</i>) variant in two siblings of other family. The patient who carried the <i>SHOC2</i> variant presented polyarthritis and serositis, while the patient with the <i>TNFRSF13B</i> variant onset with a glomerulonephritis. Those manifestations have already been described related to these genes. Variants and phenotypes are detailed in Table 1. <h3>Conclusion</h3> Around 30% pediatric patients with cSLE or LL showed at least one variant in gene related to monogenic-lupus and some of them with similar phenotypes to those already described. This fact may suggest the genetics potential contribution to the cSLE pathogenesis. Further studies are necessary to confirm these data. <h3>Reference</h3> [1]Alperin JM, Ortiz-Fernández L, Sawalha AH. Monogenic Lupus: A Developing Paradigm of Disease. Front Immunol. 2018;9:2496. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.